RegIIA: An alpha 4/7-conotoxin from the venom of Conus regius that potently blocks alpha 3 beta 4 nAChRs

Franco, Aldo, Kompella, Shiva N., Akondi, Kalyana B., Melaun, Christian, Daly, Norelle L., Luetje, Charles W., Alewood, Paul F., Craik, David J., Adams. David J. and Mari, Frank (2012) RegIIA: An alpha 4/7-conotoxin from the venom of Conus regius that potently blocks alpha 3 beta 4 nAChRs. Biochemical Pharmacology, 83 3: 419-426. doi:10.1016/j.bcp.2011.11.006

Author Franco, Aldo
Kompella, Shiva N.
Akondi, Kalyana B.
Melaun, Christian
Daly, Norelle L.
Luetje, Charles W.
Alewood, Paul F.
Craik, David J.
Adams. David J.
Mari, Frank
Title RegIIA: An alpha 4/7-conotoxin from the venom of Conus regius that potently blocks alpha 3 beta 4 nAChRs
Formatted title
RegIIA: An α4/7-conotoxin from the venom of Conus regius that potently blocks α3β4 nAChRs
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 2012-02
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.bcp.2011.11.006
Open Access Status
Volume 83
Issue 3
Start page 419
End page 426
Total pages 8
Place of publication Philadelphia, PA, U.S.A.
Publisher Elsevier
Collection year 2012
Language eng
Formatted abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) play pivotal roles in the central and peripheral nervous systems. They are implicated in disease states such as Parkinson's disease and schizophrenia, as well as addictive processes for nicotine and other drugs of abuse. Modulation of specific nAChRs is essential to understand their role in the CNS. α-Conotoxins, disulfide-constrained peptides isolated from the venom of cone snails, potently inhibit nAChRs. Their selectivity varies markedly depending upon the specific nAChR subtype/α-conotoxin pair under consideration. Thus, α-conotoxins are excellent probes to evaluate the functional roles of nAChRs subtypes.

We isolated an α4/7-conotoxin (RegIIA) from the venom of Conus regius. Its sequence was determined by Edman degradation and confirmed by sequencing the cDNA of the protein precursor. RegIIA was synthesized using solid phase methods and native and synthetic RegIIA were functionally tested using two-electrode voltage clamp recording on nAChRs expressed in Xenopus laevis oocytes. RegIIA is among the most potent antagonist of the α3β4 nAChRs found to date and is also active at α3β2 and α7 nAChRs. The 3D structure of RegIIA reveals the typical folding of most α4/7-conotoxins. Thus, while structurally related to other α4/7 conotoxins, RegIIA has an exquisite balance of shape, charge, and polarity exposed in its structure to potently block the α3β4 nAChRs.
Keyword Conus regius
Nicotinic acetylcholine receptor
NMR structure
Nicotine addiction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 16 November 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Created: Thu, 22 Dec 2011, 09:46:54 EST by Susan Allen on behalf of Institute for Molecular Bioscience